The quorum-sensing molecules farnesol/homoserine lactone and dodecanol operate via distinct modes of action in Candida albicans

Living as a commensal, Candida albicans must adapt and respond to environmental cues generated by the mammalian host and by microbes comprising the natural flora. These signals have opposing effects on C. albicans, with host cues promoting the yeast-to-hyphal transition and bacteria-derived quorum-sensing molecules inhibiting hyphal development. Hyphal development is regulated through modulation of the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, and it has been postulated that quorum-sensing molecules can affect filamentation by inhibiting the cAMP pathway. Here, we show that both farnesol and 3-oxo-C12-homoserine lactone, a quorum-sensing molecule secreted by Pseudomonas aeruginosa, block hyphal development by affecting cAMP signaling; they both directly inhibited the activity of the Candida adenylyl cyclase, Cyr1p. In contrast, the 12-carbon alcohol dodecanol appeared to modulate hyphal development and the cAMP signaling pathway without directly affecting the activity of Cyr1p. Instead, we show that dodecanol exerted its effects through a mechanism involving the C. albicans hyphal repressor, Sfl1p. Deletion of SFL1 did not affect the response to farnesol but did interfere with the response to dodecanol. Therefore, quorum sensing in C. albicans is mediated via multiple mechanisms of action. Interestingly, our experiments raise the possibility that the Burkholderia cenocepacia diffusible signal factor, BDSF, also mediates its effects via Sfl1p, suggesting that dodecanol's mode of action, but not farnesol or 3-oxo-C12-homoserine lactone, may be used by other quorum-sensing molecules

Bolometric calibration of a superfluid 3^3He detector for Dark Matter search: direct measurement of the scintillated energy fraction for neutron, electron and muon events

We report on the calibration of a superfluid $^3$He bolometer developed for the search of non-baryonic Dark Matter. Precise thermometry is achieved by the direct measurement of thermal excitations using Vibrating Wire Resonators (VWRs). The heating pulses for calibration were produced by the direct quantum process of quasiparticle generation by other VWRs present. The bolometric calibration factor is analyzed as a function of temperature and excitation level of the sensing VWR. The calibration is compared to bolometric measurements of the nuclear neutron capture reaction and heat depositions by cosmic muons and low energy electrons. The comparison allows a quantitative estimation of the ultra-violet scintillation rate of irradiated helium, demonstrating the possibility of efficient electron recoil event rejection.Comment: 17 pages, submitted to Nuc. Instr. Meth.

An analysis method for time ordered data processing of Dark Matter experiments

The analysis of the time ordered data of Dark Matter experiments is becoming more and more challenging with the increase of sensitivity in the ongoing and forthcoming projects. Combined with the well-known level of background events, this leads to a rather high level of pile-up in the data. Ionization, scintillation as well as bolometric signals present common features in their acquisition timeline: low frequency baselines, random gaussian noise, parasitic noise and signal characterized by well-defined peaks. In particular, in the case of long-lasting signals such as bolometric ones, the pile-up of events may lead to an inaccurate reconstruction of the physical signal (misidentification as well as fake events). We present a general method to detect and extract signals in noisy data with a high pile-up rate and qe show that events from few keV to hundreds of keV can be reconstructed in time ordered data presenting a high pile-up rate. This method is based on an iterative detection and fitting procedure combined with prior wavelet-based denoising of the data and baseline subtraction. {We have tested this method on simulated data of the MACHe3 prototype experiment and shown that the iterative fitting procedure allows us to recover the lowest energy events, of the order of a few keV, in the presence of background signals from a few to hundreds of keV. Finally we applied this method to the recent MACHe3 data to successfully measure the spectrum of conversion electrons from Co57 source and also the spectrum of the background cosmic muons

What it takes to measure a fundamental difference between dark matter and baryons: the halo velocity anisotropy

Numerous ongoing experiments aim at detecting WIMP dark matter particles from the galactic halo directly through WIMP-nucleon interactions. Once such a detection is established a confirmation of the galactic origin of the signal is needed. This requires a direction-sensitive detector. We show that such a detector can measure the velocity anisotropy beta of the galactic halo. Cosmological N-body simulations predict the dark matter anisotropy to be nonzero, beta~0.2. Baryonic matter has beta=0 and therefore a detection of a nonzero beta would be strong proof of the fundamental difference between dark and baryonic matter. We estimate the sensitivity for various detector configurations using Monte Carlo methods and we show that the strongest signal is found in the relatively few high recoil energy events. Measuring beta to the precision of ~0.03 will require detecting more than 10^4 WIMP events with nuclear recoil energies greater than 100 keV for a WIMP mass of 100 GeV and a 32S target. This number corresponds to ~10^6 events at all energies. We discuss variations with respect to input parameters and we show that our method is robust to the presence of backgrounds and discuss the possible improved sensitivity for an energy-sensitive detector.Comment: 15 pages, 8 figures, accepted by JCAP. Matches accepted versio

Camphor and Eucalyptol-Anticandidal Spectrum, Antivirulence Effect, Efflux Pumps Interference and Cytotoxicity.

Candidaalbicans represents one of the most common fungal pathogens. Due to its increasing incidence and the poor efficacy of available antifungals, finding novel antifungal molecules is of great importance. Camphor and eucalyptol are bioactive terpenoid plant constituents and their antifungal properties have been explored previously. In this study, we examined their ability to inhibit the growth of different Candida species in suspension and biofilm, to block hyphal transition along with their impact on genes encoding for efflux pumps (CDR1 and CDR2), ergosterol biosynthesis (ERG11), and cytotoxicity to primary liver cells. Camphor showed excellent antifungal activity with a minimal inhibitory concentration of 0.125-0.35 mg/mL while eucalyptol was active in the range of 2-23 mg/mL. The results showed camphor's potential to reduce fungal virulence traits, that is, biofilm establishment and hyphae formation. On the other hand, camphor and eucalyptol treatments upregulated CDR1;CDR2 was positively regulated after eucalyptol application while camphor downregulated it. Neither had an impact on ERG11 expression. The beneficial antifungal activities of camphor were achieved with an amount that was non-toxic to porcine liver cells, making it a promising antifungal compound for future development. The antifungal concentration of eucalyptol caused cytotoxic effects and increased expression of efflux pump genes, which suggests that it is an unsuitable antifungal candidate

Azole Resistance of Environmental and Clinical Aspergillus fumigatus Isolates from Switzerland.

Aspergillus fumigatus is a ubiquitous opportunistic pathogen. This fungus can acquire resistance to azole antifungals due to mutations in the azole target (cyp51A). Recently, cyp51A mutations typical for environmental azole resistance acquisition (for example, TR <sub>34</sub> /L98H) have been reported. These mutations can also be found in isolates recovered from patients. Environmental azole resistance acquisition has been reported on several continents. Here we describe, for the first time, the occurrence of azole-resistant A. fumigatus isolates of environmental origin in Switzerland with cyp51A mutations, and we show that these isolates can also be recovered from a few patients. While the TR <sub>34</sub> /L98H mutation was dominant, a single azole-resistant isolate exhibited a cyp51A mutation (G54R) that was reported only for clinical isolates. In conclusion, our study demonstrates that azole resistance with an environmental signature is present in environments and patients of Swiss origin and that mutations believed to be unique to clinical settings are now also observed in the environment

The structure of western Serra do Curral, Quadrilátero Ferrífero, and tectonic control of the high-grade iron hard bodies

The structure of western Serra do Curral, Quadrilátero Ferrífero, represents the partial exposure of a syncline that verges to NNW - Piedade Syncline. This regional structure has parasitic folds denominated as B1A which are refolded by folds B1B that also have vergence to NNW. Both of them have ENE-WSW direction, are non-cylindrical folds and configure an interference pattern that is similar to Type 3 from Ramsay. This refolding occur during progressive deformation. The occurrence of highgrade magnetitic-martitic accumulation (> 64% Fe) of medium size (~ 100 Mt) is controlled by the combination of these folds and high angle thrust fault, both with the same direction. Above these structures, there is a development of folds with NNWSSE direction and WSW vergence (B2 folds). These folds are restricted to the B1 limbs and they configure an interference pattern named "abbuting fold". The age obtained by U/Pb SHRIMP on monazite grains is 2034 ± 11 Ma. The monazite grains occur on textural balance with the iron oxide from high-grade accumulations. This age corresponds to the formation timing of the high-grade bodies and suggests that the mineralization process is contemporary to the regional metamorphic peak of Quadrilátero Ferrífero

On the direct search for spin-dependent WIMP interactions

We examine the current directions in the search for spin-dependent dark matter. We discover that, with few exceptions, the search activity is concentrated towards constraints on the WIMP-neutron spin coupling, with significantly less impact in the WIMP-proton sector. We review the situation of those experiments with WIMP-proton spin sensitivity, toward identifying those capable of reestablishing the balance.Comment: 7 pages, 4 figure

Direct Search for Low Mass Dark Matter Particles with CCDs

A direct dark matter search is performed using fully-depleted high-resistivity CCD detectors . Due to their low electronic readout noise (RMS ~ 7 eV) these devices operate with a very low detection threshold of 40 eV, making the search for dark matter particles with low masses (~ 5 GeV) possible. The results of an engineering run performed in a shallow underground site are presented, demonstrating the potential of this technology in the low mass region